Rainer H Müller

Freie Universität Berlin, Berlín, Berlin, Germany

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Publications (104)302.35 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: For the development of ultra-small NLC (usNLC) the determination of the required HLB (hydrophilic lipophilic balance) was found to be a suitable method, i.e., usNLC with a size below 50 nm were obtained by this method. Loading with 5% (w/w) coenzyme Q10 (Q10) led to usNLC with a size of about 85 nm. In comparison to classical NLC with a size of 230 nm and a nanoemulsion with similar size, the Q10 loaded usNLC show a higher release, a higher antioxidant capacity, and a better skin penetration for Q10. The reason for this is a flip–flop core–shell structure of the lipid matrix, i.e., the oil with dissolved active is surrounding the solid lipid based core. As the flip–flop structure was probably achieved by admixing high contents of liquid lipid, oil enriched usNLC might represent a novel and promising carrier system for the improved delivery of lipophilic actives.
    International Journal of Pharmaceutics 12/2014; 477(1). · 3.99 Impact Factor
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    ABSTRACT: Alkyl polyglycosides (APGs) represent a group of nonionic tensides with excellent skin compatibility. Thus they seem to be excellent stabilizers for lipid nanoparticles for dermal application. To investigate this, different APGs were selected to evaluate their influence on the formation and characteristics of solid lipid nanoparticles (SLN). Contact angle analysis of the aqueous solutions/dispersions of the APGs on cetyl palmitate films revealed good wettability for all APG surfactants. Cetyl palmitate based SLN were prepared by hot high pressure homogenization and subjected to particle size, charge and inner structure analysis. 1% of each APG was sufficient to obtain SLN with a mean size between 150nm and 175nm and a narrow size distribution. The zeta potential in water was ∼ -50mV; the values in the original medium were distinctly lower, but still sufficient high to provide good physical stability. Physical stability at different temperatures (5°C, 25° and 40°C) was confirmed by a constant particle size over an observation period of 90 days in all dispersions. In comparison to SLN stabilised with classical surfactants, e.g. Polysorbate, APG stabilised SLN possess a smaller size, improved physical stability and contain less surfactant. Therefore, the use of APGs for the stabilization of lipid nanoparticles is superior in comparison to classical stabilizers. Further, the results indicate that the length of the alkyl chain of the APG influences the diminution efficacy, the final particle size and the crystallinity of the particles. APGs with short alkyl chain led to a faster reduction in size during high pressure homogenization, to a smaller particle size of the SLN and to a lower recrystallization index, i.e. to a lower crystallinity of the SLN. The crystallinity of the SLN increased with an increase in the alkyl chain length of APGs. Therefore, by using the tested APGs differing in the alkyl chain length, not only small sized and physically stable but also SLN with different sizes and crystallinity can be obtained. An optimised selection of these stabilizers might therefore enable the production of lipid nanoparticles with "tailor-made" properties.
    International Journal of Pharmaceutics 08/2014; · 3.99 Impact Factor
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    ABSTRACT: After use in oral pharmaceutical products, nanocrystals are meanwhile applied to improve the dermal penetration of cosmetic actives (e.g., rutin, hesperidin) and of drugs. By now, nanocrystals are only dermally applied made from poorly soluble actives. The novel concept is to formulate nanocrystals also from medium soluble actives, and to apply a dermal formulation containing additionally nanocrystals. The nanocrystals should act as fast dissolving depot, increase saturation solubility and especially accumulate in the hair follicles, to further increase skin penetration. Caffeine was used as model compound with relevance to market products, and a particular process was developed for the production of caffeine nanocrystals to overcome the supersaturation related effect of crystal growth and fiber formation - typical with medium soluble compounds. It is based on low energy milling (pearl milling) in combination with low dielectric constant dispersion media (water-ethanol or ethanol-propylene glycol mixtures) and optimal stabilizers. Most successful was Carbopol(®) 981 (e.g., 20% caffeine in ethanol-propylene glycol 3:7 with 2% Carbopol, w/w). Nanocrystals with varied sizes can now be produced in a controlled process, e.g., 660nm (optimal for hair follicle accumulation) to 250nm (optimal for fast dissolution). The short term test proved stability over 2 months of the present formulation being sufficient to perform in vivo testing of the novel concept.
    International Journal of Pharmaceutics 05/2014; · 3.99 Impact Factor
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    ABSTRACT: Polyhydroxy surfactants are nonionic ethylene oxide free stabilizers known for their complimentary dermatological properties and favorable environmental profile. The aim of this study was to develop solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants varying in the chemical structure and to investigate the influence of the surfactants on the characteristics of the particles. Particles were produced by hot high pressure homogenization and the physico-chemical properties, e.g. contact angle, particle size, size distribution, zeta potential and crystallinity were determined. Results showed that the chemical structure of the surfactants influences the contact angle, particle size and crystallinity. Furthermore, the low surfactants concentration used (1% (w/w)) allowed the formation of the particles with a mean size below 200 nm, polydispersity index lower than 0.1 and sufficient physical stability for at least 6 months. As postulated by the zeta potential analysis stabilization ability of the surfactants was attributed to the superposition of electrostatic and steric effect which complement each other. All SLN formulations consisted of the same lipid matrix, but were found to possess different crystallinity indices. These differences are obviously created by the differences in the chemical structure of the surfactants. Therefore, the polyhydroxy surfactants investigated in this study can be judged to be novel suitable stabilizers for the formulation of well-skin tolerable SLN. The use of specific chemical structures of the surfactants can be used for the production of “tailor-made” SLN in the future.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 03/2014; 444:15–25. · 2.11 Impact Factor
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    ABSTRACT: The ARTcrystal(®) process is a new approach for the production of drug nanocrystals. It is a combination of a special pre-treatment step with subsequent high pressure homogenization (HPH) at low pressures. In the pre-treatment step the particles size is already reduced to the nanometer range by use of the newly developed ART MICCRA rotor-stator system. In this study, the running parameters for the ART MICCRA system are systematically studied, i.e. temperature, stirring speed, flow rate, foaming effects, size of starting material, valve position from 0° to 45°. The antioxidant rutin was used as model drug. Applying optimized parameters, the pre-milling yielded already a nanosuspension with a photon correlation spectroscopy (PCS) diameter of about 650nm. On lab scale production time was 5min for 1L nanosuspension (5% rutin content), i.e. the capacity of the set up is also suitable for medium industrial scale production. Compared to other nanocrystal production methods (bead milling, HPH etc.), similar sizes are achievable, but the process is more cost-effective, faster in time and easily scale-able, thus being an interesting novel process for nanocrystal production on lab and industrial scale.
    International Journal of Pharmaceutics 02/2014; · 3.99 Impact Factor
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    ABSTRACT: Nanocrystals are meanwhile applied to increase the dermal penetration of drugs, but were applied by now only to poorly soluble drugs (e.g. 1-10 μg/ml). As a new concept nanocrystals from medium soluble actives were produced, using caffeine as model compound (solubility 16 mg/ml at 20°C). Penetration should be increased by a) further increase in solubility and b) mainly by increased hair follicle targeting of nanocrystals compared to pure solution. Caffeine nanocrystal production in water lead to pronounced crystal growth. Therefore the stability of nanocrystals in water-ethanol (1:9) and ethanol-propylene glycol (3:7) mixtures with lower dielectric constant D was investigated, using various stabilizers. Both mixtures in combination with Carbopol(®) 981 (non-neutralized) yielded stable nanosuspensions over 2 months at 4°C and room temperature. Storage at 40°C lead to crystal growth, attributed to too strong solubility increase, supersaturation and Ostwald ripening effects. Stability of caffeine nanocrystals at lower temperatures could not only be attributed to lower solubility, because the solubilities of caffeine in mixtures and in water are not that much different. Other effects such as quantified by reduced dielectric constant D, and specific interactions between dispersion medium and crystal surface seem to play a role. With the 2 mixtures and Carbopol(®) 981, a basic formulation composition for this type of nanocrystals has been established, to be used in the in vivo proof of principle of the new concept.
    European Journal of Pharmaceutics and Biopharmaceutics. 01/2014;
  • Biswadip Sinha, Rainer H Müller, Jan P Möschwitzer
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    ABSTRACT: Cavi-precipitation process is a combinative particle size reduction technology based on solvent-anti-solvent precipitation coupled high pressure homogenization (HPH). The cavi-precipiation can be used for the efficient production of drug nanocrystals (NC) with improved dissolution rate leading to better bioavailability. The work presented here demonstrates the advantage of cavi-precipitation process over the standard HPH processes and standard combination process (decoupled process) where precipitation is performed outside the homogenizer. The model compound ibuprofen (IBP) was solubilized in isopropanol (IPA) to constitute the solvent phase and mixed with the anti-solvent phase (0.1% (w/v) hydroxypropyl methylcellulose with 0.2% (w/v) sodium dodecyl sulphate) at different ratios to carry out the precipitation step. IBP-IPA-Water composition was selected from ternary diagram for a highly supersaturated zone to obtain smaller size particles. The mean particle size [d(0.5)] obtained by this process (300nm) was much smaller when compared to that obtained from the decoupled process (1.5μm). Optimization of the solvent-anti-solvent ratio and drug concentration was necessary to achieve a smaller particle size. PXRD and DSC results revealed that the solid state properties of the original IBP and the prepared NC samples by cavi-precipitation samples were similar.
    International Journal of Pharmaceutics 10/2013; · 3.99 Impact Factor
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    ABSTRACT: Abstract Objective: To prepare stable and easy to handle formulation of solid lipid nanoparticles (SLNs) by freeze-drying with or without cryoprotectants, as appropriate. Materials and methods: SLNs were freeze-dried without cryoprotectants or with cryoprotectants in quantities selected by freeze-thaw test (sucrose, glucose) or literature search (trehalose, maltose). Appearance, re-dispersability and size distribution of re-dispersed samples were evaluated. Results: SLN could be freeze-dried using 10% sucrose, trehalose or maltose. Trehalose was effective in protecting one of presented formulations that was already very stable on its own; its efficiency in protecting other two formulations was limited. Discussion: Our results are in line with various reports of successful freeze-drying of SLN, but considering the stability of original dispersions, no improvement was achieved. Conclusion: We confirmed that trehalose is among the most suitable cryoprotectant for SLN, however it did not improve shelf-life of the most stable formulation.
    Pharmaceutical Development and Technology 10/2013; · 1.33 Impact Factor
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    ABSTRACT: Abstract Nicergoline, a poorly soluble active pharmaceutical ingredient, possesses vaso-active properties which causes peripheral and central vasodilatation. In this study, nanocrystals of nicergoline were prepared in an aqueous solution of polysorbate 80 (nanosuspension) by using four different laboratory scale size reduction techniques: high pressure homogenization (HPH), bead milling (BM) and combination techniques (high pressure homogenization followed by bead milling HPH + BM, and bead milling followed by high pressure homogenization BM + HPH). Nanocrystals were investigated regarding to their mean particles size, zeta potential and particle dissolution. A short term physical stability study on nanocrystals stored at three different temperatures (4, 20 and 40 °C) was performed to evaluate the tendency to change in particle size, aggregation and zeta potential. The size reduction technique and the process parameters like milling time, number of homogenization cycles and pressure greatly affected the size of nanocrystals. Among the techniques used, the combination techniques showed superior and consistent particle size reduction compared to the other two methods, HPH + BM and BM + HPH giving nanocrystals of a mean particle size of 260 and 353 nm, respectively. The particle dissolution was increased for any nanocrystals samples, but it was particularly increased by HPH and combination techniques. Independently to the production method, nicergoline nanocrystals showed slight increase in particle size over the time, but remained below 500 nm at 20 °C and refrigeration conditions.
    Drug Development and Industrial Pharmacy 07/2013; · 1.54 Impact Factor
  • Jaime Salazar, Rainer H Müller, Jan P Möschwitzer
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    ABSTRACT: Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions. The need for micronized starting material and long process times are their evident disadvantages. Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques. The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization. In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed. Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500 bar. For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772 nm and volume-based size distribution values of 2.686 μm (d50%) and 14.423 μm (d90%). The use of pre-treated material (10:1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236 nm and volume-based size distribution values of 0.131 μm (d50%) and 0.285 μm (d90%). These results were markedly improved compared to the standard process. The nanosuspensions were further transferred into tablet formulations. Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates. Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying > freeze-drying > wet granulation. The best drug release (90% within 10 minutes) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former. In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10 min. The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals. A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 04/2013; · 2.61 Impact Factor
  • Jaime Salazar, Rainer H Müller, Jan P Möschwitzer
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    ABSTRACT: The nanosizing of poorly soluble drugs as a formulation strategy can eventually enhance their dissolution rate and bioavailability. Standard comminution techniques such as high-pressure homogenization (HPH) or wet bead milling have limitations in reaching the desired mean particle size. Combinative methods have been developed to overcome these limitations. Combinations of a bottom-up step (freeze-drying or spray drying) with HPH (the so-called H 96 and H 42 technologies, respectively) are examples of combinative particle-size-reduction technologies. The precipitation step modifies the drug structure to obtain a brittle starting material for the following homogenization process. Previous experiments using the H 96 technology have shown a relation between the bottom-up conditions and the final particle size after the top-down step. Employing the H 42 process, the poorly soluble drug glibenclamide was dissolved in ethanol, containing different amounts of surfactant. The drug solution was then spray dried. Subsequently, the drug powders were homogenized using the HPH technique. The nanosuspensions produced with the spray-dried powders (high drug concentrations, standard surfactant concentration) had a smaller particle size and a narrower size distribution compared with the unmodified drug. The best sample had a 236 nm mean particle size (observed using photon correlation spectroscopy) and laser diffractometry values of 0.131 µm (D50) and 0.285 µm (D90) after 20 cycles of homogenization. The results were compared with the reduction effectiveness of a previous study employing the H 96 combinative process. Both combinative technologies can be successfully applied for the production of very small drug nanocrystals. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 02/2013; · 3.13 Impact Factor
  • Biswadip Sinha, Rainer H Müller, Jan P Möschwitzer
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    ABSTRACT: The solubility dependent bioavailability problem has become a major hurdle in drug development processes. Drug nanocrystals have been widely accepted by the pharmaceutical industry to improve the bioavailability of poorly water soluble compounds. Top-down and bottom-up technologies are the two primary technical approaches of drug nanocrystal production. Though the top-down approach has been hugely successful on the commercial front, it has some inherent drawbacks that necessitate the emergence of alternate approaches. The bottom-up approach has not yet been established as a successful commercial technology. However, it has the potential to produce small size drug nanocrystals with less energy demanding processes. The bottom-up approach is commonly known as precipitation technique. It would be possible to stabilize particles at an early stage of precipitation and to generate drug nanocrystals. In the first part of this review article, we have discussed various bottom-up technologies that are currently in use. This has been followed by description and analysis of various process parameters that can affect the final particle size of the drug nanocrystals.
    International Journal of Pharmaceutics 01/2013; · 3.99 Impact Factor
  • Cornelia M Keck, Rainer H Müller
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    ABSTRACT: There is an increasing discussion about potential toxicity of nanoparticles (nanotoxicity). A classification system is proposed classifying the nanoparticles in 4 classes (I to IV) from low/no risk to high risk. It is based on the nanoparticle size (>/< 100 nm) and size-related differences in interaction with human cells, and on biodegradability/non-biodegradability in the body. This classification is superimposed by biocompatibility (B) and non-biocompatibility (NB) of the nanoparticle surface, resulting in a total of 8 classes from I-B (best tolerated) to IV-NB (highest potential risk). The classification should help as a guideline in pharmaceutical formulation development, but also as a guide for risk assessment in other product areas and environmental exposure.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 01/2013; · 3.15 Impact Factor
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    ABSTRACT: Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment. In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid. Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH. In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility. Five different stabilizers [polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt] possessing different stabilization mechanism were investigated. The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity. A short-term stability study was performed storing the differently stabilized nanoparticles at 4°C and room temperature. PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm. PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability. However, PVP is the most efficient polymer to stabilize curcumin nanoparticle. This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 10/2012; · 3.13 Impact Factor
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    ABSTRACT: This study aimed to examine the long-term physical stability of quercetin nanocrystals produced by three methods. Quercetin nanocrystals were prepared by high pressure homogenization, bead milling and cavi-precipitation. The nanocrystals produced by these methods were compared for particle size, saturation solubility and dissolution of the drug particles, and were subjected to stability testing. The X-ray diffraction study and microscopic pictures taken under polarized light indicated the crystalline nature of the nanocrystals produced by the three methods. As the crystalline state is relatively more stable than the amorphous state, a good physical stability was expected from the quercetin nanocrystals prepared. The high-pressure homogenized and bead-milled quercetin nanocrystals showed excellent physical stability when stored under refrigeration (4±2°C) and at room temperature (25±2°C) for 180 days. The dissolution properties were not significantly affected on storage at room temperature. However, increase in the storage temperature to 40±2°C led to physical instability. On the other hand, the cavi-precipitated quercetin nanocrystals exhibited a lower stability than the bead-milled and homogenized formulations and did not show the optimum zeta potential values as well. In the case of cavi-precipitated nanocrystals, recrystallization and agglomeration were responsible for the increasing particle size besides the Ostwald ripening phenomenon. The solvents used during cavi-precipitation might have competed with the surfactant for hydration leading to a partial dehydration of the surfactant, which subsequently affected the stability of the quercetin nanocrystals. High-pressure homogenized and bead-milled quercetin nanocrystals showed better physical stability than the cavi-precipitated ones. Freeze drying immediately after nanocrystal production can help to prevent their agglomeration and thus improve physical stability.
    The Journal of pharmacy and pharmacology. 10/2012; 64(10):1394-402.
  • Jan P Möschwitzer, Rainer H Müller
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    ABSTRACT: Context: This article discusses the downstream processing of nanosuspensions into oral solid dosage forms. Objective: Various factors influencing the release kinetics of various pellet formulations containing drug nanocrystals have been evaluated. The effects of binder types, drug content and pellet type on the in-vitro dissolution profiles were investigated. Materials and methods: Hydrocortisone acetate (HCA) was nanosized by using a piston gap homogenizer Micron Lab 40. The nanosuspension was admixed to various binder solutions based on chitosan chloride, polyvinyl alcohol, hydroxypropyl methylcellulose or polyvinylpyrrolidone (PVP) and sprayed on sugar beads using fluidized bed coating. For comparison, matrix cores have also been prepared using the extrusion-spheronization process. An enteric top coating was applied onto both pellet types. All pellet formulations have been tested In in-vitro dissolution studies. Results and discussion: HCA nanosuspensions were compatible with all binders tested except for PVP. Various suspensions could be successfully transferred into spray coated pellets as well as matrix cores including a top coating. The different binder types have influenced the stability of the nanosuspensions, the zeta potential of the drug nanocrystals as well as the dissolution profiles of the final solid dosage forms. Conclusion: Nanosuspensions can be easily processed into various pellet formulations. Spray coating with water-soluble binders is recommended for high dose drugs. This technology is also more variable with respect to the drug load In the final dosage form. Matrix cores can be beneficial for highly water-insoluble formulations, especially when only relatively low doses are needed.
    Drug Development and Industrial Pharmacy 07/2012; · 1.54 Impact Factor
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    ABSTRACT: Nanosizing is a non-specific approach to improve the oral bioavailability of poorly soluble drugs. The decreased particle size of these compounds results in an increase in surface area. The outcome is an increased rate of dissolution, which can lead to a better oral absorption. Standard approaches are bottom-up and top-down techniques. Combinative technologies are relatively new approaches, and they can be described as a combination of a bottom-up process followed by a top-down step. The work presented in this paper can be described as a combination of a non-aqueous freeze drying step (bottom-up), followed by wet ball milling or high pressure homogenization (top-down) to produce fine drug nanocrystals. The crystal habit of the model drug glibenclamide was modified by freeze drying from dimethyl sulfoxide (DMSO)/tert-butanol (TBA) solvent mixtures using different ratios. The resulting drug powders were characterized by scanning electron microscopy (SEM) as well as by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). It was shown that the combinative approach can significantly improve the particle size reduction effectiveness of both top-down methods over conventional approaches. Drug lyophilization using DMSO:TBA in 25:75 and 10:90 v/v ratios resulted in a highly porous and breakable material. The milling time to achieve nanosuspensions was reduced from 24h with the jet-milled glibenclamide to only 1h with the modified starting material. The number of homogenization cycles was decreased from 20 with unmodified API to only 5 with the modified drug. The smallest particle size, achieved on modified samples, was 160nm by wet ball milling after 24h and 355nm by high pressure homogenization after 20 homogenization cycles at 1500bar.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 01/2012; 81(1):82-90. · 3.15 Impact Factor
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    Cornelia M Keck, Mirko Jansch, Rainer H Müller
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    ABSTRACT: Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern), typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface). The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics.
    Pharmaceutics 01/2012; 5(1):36-68.
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    ABSTRACT: This research aimed to evaluate the suitability of lipids for the manufacture of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with the hydrophilic drug, didanosine (DDI). The crystalline state and polymorphism of lipids with the best-solubulizing potential for DDI was investigated using differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). DSC and WAXS were also used to determine potential interactions between the bulk lipids and DDI. Precirol® ATO 5 and Transcutol® HP showed the best-solubilizing potential for DDI. Precirol® ATO 5 exists in the β-modification before heating; however, a mixture of both α- and β-modifications were detected following heating. Addition of Transcutol® HP to Precirol® ATO 5 changes the polymorphism of the latter from the β-modification to a form that exhibits coexistence of the α- and β-modifications. DDI exists in a crystalline state when dispersed at 5% (w/w) in Precirol® ATO 5 or in a Precirol® ATO 5/Transcutol® HP mixture. DSC and WAXS profiles of DDI/bulk lipids mixture obtained before and after exposure to heat revealed no interactions between DDI and the lipids. Precirol® ATO 5 and a mixture of Precirol® ATO 5 and Transcutol® HP may be used to manufacture DDI-loaded SLN and NLC, respectively.
    Journal of Pharmaceutical Sciences 12/2011; 100(12):5185-96. · 3.13 Impact Factor
  • Saša Nikolićć, Sven Gohla, Rainer H Müller
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    ABSTRACT: Lipid nanoparticles possess a solid particle matrix ideal for the incorporation of lipophilic UV radiation (UVR) filters. Incorporation of the UVR filters into the nanoparticles increases their UVR protective effect compared with oil-in-water emulsions. Due to the solid state of the particle matrix, the release of the UV filters is lower compared with emulsions, thus the UVR filters remain longer on the skin and penetration into the skin and related side effects are reduced. The risk of skin penetration, with potential side effects, of very small-sized particulate UVR protectants, such as titanium dioxide (∼15 nm), has not yet been excluded. These particulates can also be incorporated into the lipid nanoparticles (∼300 nm), the firm enclosure inside the nanoparticles excludes penetration into the skin. At the same time, UVR protection is increased. Lipid nanoparticles can be produced on industrial scale by high-pressure homogenization; all excipients are regulatory authority-accepted. Production of dermal products is proven by cosmetic products already on the market.
    Expert Review of Dermatology 09/2011; 6(5):501-507.

Publication Stats

2k Citations
302.35 Total Impact Points

Institutions

  • 1992–2014
    • Freie Universität Berlin
      • • Institute of Pharmacy
      • • Division of Pharmaceutical Technology
      Berlín, Berlin, Germany
  • 2013
    • University of Camerino
      Camerino, The Marches, Italy
  • 2011–2012
    • Nanyang Technological University
      • School of Mechanical and Aerospace Engineering (MAE)
      Singapore, Singapore
  • 2010
    • University of Sharjah
      • College of Pharmacy
      Ash Shāriqah, Ash Shāriqah, United Arab Emirates
    • Universidade Fernando Pessoa
      • Faculty of Health Sciences
      Porto, Distrito do Porto, Portugal
  • 2009–2010
    • Charité Universitätsmedizin Berlin
      • Institute of Microbiology and Hygiene
      Berlin, Land Berlin, Germany
    • Central Drug Research Institute
      • Pharmaceutics Division (CDRI)
      Lucknow, Uttar Pradesh, India
  • 2007–2009
    • Mahidol University
      • Department of Pharmacy
      Bangkok, Bangkok, Thailand
  • 2005
    • Hochschule für Gesundheit und Medizin
      Berlín, Berlin, Germany